Triethylamine → tert-butyl (4S,7S,10aS)-7-cyano-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate

HRID 529485Notes

Reaction equation

HRID 529485 reaction equation
C(N(CC)CC)C.[C:8]([C@H:11]1[N:21]2[C@@H:15]([S:16][CH2:17][CH2:18][C@H:19]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[C:20]2=[O:22])[CH2:14][CH2:13][CH2:12]1)(=O)[NH2:9].C(OC(C(F)(F)F)=O)(C(F)(F)F)=O>C(Cl)Cl>[C:8]([C@H:11]1[N:21]2[C@@H:15]([S:16][CH2:17][CH2:18][C@H:19]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:28])([CH3:27])[CH3:29])[C:20]2=[O:22])[CH2:14][CH2:13][CH2:12]1)#[N:9]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 68311221tert-butyl (4S,7S,10aS)-7-carbamoyl-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate

Product 1

HCID 86706201tert-butyl (4S,7S,10aS)-7-cyano-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamateYield 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Triethylamine (58.8 mg, 0.581 mmol) was added to a 0° C. solution of tert-butyl (4S,7S,10aS)-7-carbamoyl-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate (57 mg, 0.17 mmol) in DCM (1.2 mL). TFAA (52.3 mg, 0.249 mmol) was then slowly added to the reaction. The ice bath was removed and the reaction mixture was left to stir at rt for 1 hr. The reaction was diluted with DCM (2 mL) and quenched by the addition of aqueous 10% Na2CO3 (2 mL). The aqueous phase was isolated and extracted with DCM (2 mL). All organic phases were combined, dried over MgSO4, filtered and concentrated. The crude product was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-100% EtOAc/Hex to give tert-butyl (4S,7S,10aS)-7-cyano-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate (36 mg, 0.11 mmol, 67% yield) as a light yellow solid. Anal. Calcd. for C15H23N3O3S m/z 325.4. found: 326.3 (M+H)+.

Workup

  1. customThe ice bath was removed
  2. waitthe reaction mixture was left
  3. additionThe reaction was diluted with DCM (2 mL)
  4. customquenched by the addition of aqueous 10% Na2CO3 (2 mL)
  5. customThe aqueous phase was isolated
  6. extractionextracted with DCM (2 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified
  11. washeluting with a gradient of 0-100% EtOAc/Hex

Sources & evidence

ORD record
ord-17d9d8f0ace945a5a5bfeeb80d65486d
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

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